The objective of this proposal is to define the actions of gastrointestinal hormones on the growth and drug metabolism activity of colon tumors. We will attempt to define the influence of gastrointestinal hormones on the efficacy of chemotherapeutic control of colon tumors and on the activation of carcinogens by the colon. This objective will enable us to specify the regulatory role of intestinal substances in colonic carcinogenesis as well as the efficacy of chemotherapy. We will resolve the colon drug metabolism system into its components and determine the modifying effects of gastrointestinal hormones on the distribution of multiple forms of colonic cytochrome P-450. We will also define the response of colonic cytochrome P-450 reductase to gastrointestinal hormones, and determine the effects of gastrointestinal hormones on the development, growth rate, and response to chemotherapeutic agents of colon tumor cells maintained in tissue culture or of transplantable tumors in host animals. We will thus define the role that gastrointestinal hormones and the drug metabolism system of colon and colon tumors play in carcinogenesis and in cancer control. We will continue our initial studies focusing on gastrin and then expand them to include other gastrointestinal hormones and tissue substances.